Olfaction plays a key role in an individual's response to the environment. Odors can influence the assessment of air quality and serve as warning agents. Odors also play a role as appetitive or approach stimuli. They have considerable importance in the perception of flavor and guiding food choice, they influence perceptions of health and mood and they can elicit approach or avoidance of people, places or things. In each of these situations an individual's personal capabilities to perceive the odor environment will determine the response that is made. Considerable evidence supports the claim that continued exposure to odorants in the short-term produces a reduction in sensitivity to that odorant, or adaptation. Laboratory studies of olfactory perception following odorant exposure typically show a reduction in sensitivity or perceived intensity to the odorant; however, just the reverse can occur; exposure can sensitize individuals. Furthermore, there is considerable variation in the perception of odors by people. Genes, environmental, sensory and cognitive factors all interact to produce and modify this variation. Research has been designed and executed to explore olfaction in humans and other animals (as model systems) at each of these levels of analysis. The proposed research has its foundation in psychophysical, electrophysiological, neuroanatomical and genetic strategies in an attempt to reveal mechanisms underlying olfaction. The approach is based on the premise that studies of the extremes of natural variation can lead to an understanding of the normal processess underlying olfaction. Inability to smell different odors (specific anosmias) provides the specific foundation for our studies. The causes of specific anosmia are not known, but may have a genetic component, suggesting that, by analogy to color blindness, specific anosmia results from defects in the genes encoding the olfactory receptor proteins. However, in contrast to color blindness, which is stable throughout life, specific anosmias can be reversed by exposure to the odorant. Using psychophysics and neuroanatomy, the proposed research will determine (i) whether induced sensitivity to odors differs from normal olfaction, (ii) whether the same odor quality emerges once sensitivity to it and related compounds has been induced, (iii) whether there are any non-odorous compounds that can block the perception of odors, (iv) in a model of specific anosmia, determine some of the regions in the brain that are affected by reversal of the anosmia, and (v) to localize the population of olfactory neurons that provide the input into the activated regions of brain.